The potential for the use of exhaled breath as a diagnostic tool has long been recognized. Recently, researchers have shown that the chemical composition of expired breath can be an accurate, timely, and painless indicator of the health of an individual. See Phillips, M. et al., J. Chromatography (1999), B729, 75, hereby incorporated by reference herein. For example, a number of exhaled gases such as ammonia, nitric oxide, aldehydes and ketones have been associated with kidney and liver malfunction, asthma, diabetes, cancer, and ulcers. (Alving, K et al., Eur. Respir. J. (1993), 6, 1368; Paredi, P. et al., Chest (1999), 116, 1007; and Atherton, J., Gut (1994), 35, 723.) Other exhaled compounds like ethane, butane, pentane, and carbon disulfide have been connected to abnormal neurological conditions, including schizophrenia. (Phillips, M. et al., J. Clin. Pathol. (1993), 46, 861; and Phillips, M. et al., J. Clin. Pathol. (1995), 48, 466).
There is a relatively long history of using light absorption and emission by molecules as a means for qualitatively identifying which molecules are present in a mixture, and quantitatively determining what concentration of each is present. Commonly, molecules with two or more atoms show distinct absorptions in the infrared region of the spectrum, generally defined as light with a wavelength between 1 μm and 15 μm (11 μm=10−6 m). The detailed characteristics of these “fingerprint” absorptions can be extremely sharp at low pressure for molecules that are in the gas phase, enabling both the qualitative and quantitative assays with very high selectivity.
A large number of industrial pollutant gases such as NO, NO2, NH3, SO2, and CH4 have also been readily detected using laser spectroscopy. Such gases are often detected in high concentrations at their sources and in very low concentrations in ambient atmosphere and stratosphere. One example is nitric oxide, found at very high concentrations in automobile emissions at the tailpipe, but detected at level of only ppm or less in the atmosphere. By characterizing the optical absorptivity of a sample of known concentration, the concentration of an unknown sample can then be determined. In order to facilitate such determinations, various techniques have emerged over the years allowing the accumulation of the required spectroscopic parameters for a wide variety of molecular gases. For example, development of conventional measurements of light throughput, calorimetry, cavity-ring down spectroscopy, (see O'Keefe, A. et al., Rev. Sci. Instrum. (1988) 59, 2544 and Scherer, J. J. et al., Chem. Rev. (1997), (Washington, D.C.) 97, 25.), and thermal distortion spectroscopy (see Bailey, R. T. et al., in Photoacoustic, Photothermal, and Photochemical Processes, Topics in Current Physics, ed. Hess, P. (Springer, Berlin), (1989) Vol. 46, pp. 37–60) have greatly aided such endeavors. In particular, ultra low-absorption measurements using calorimetric techniques, thus allowing sub-ppb detection of many gaseous components, have been shown to be widely applicable (see Patel, C. K. N. in Monitoring Toxic Substances, ACS Symposium Series, ed. Schuetzle, D. (Am. Chem. Soc., Washington, D.C.), (1978), Vol. 94, pp. 177–194).
Recently, Narasimhan et al. (Proc. Natl. Acad. Sci. U.S.A. (2001), 98, 4617, hereby incorporated by reference herein) showed that optoacoustic spectroscopic analysis of ammonia levels in patients with end-stage renal disease during hemodialysis could be correlated with blood urea nitrogen (BUN) and creatinine levels. Such a correlation allowed a means for assessment of nitrogenous waste loading in a patient's bloodstream in real time, as compared to a 24-hour (or more) delay for standard blood sample analysis for blood urea nitrogen and blood creatinine levels.
Many of these technologies are complex, expensive and difficult to calibrate. They have not been economically adapted for individual health care use. It has been suggested, however, that self-administered breath alcohol tests could be used (See, Brown et al. U.S. Pat. No. 5,303,575) by multiple individuals at bars or other locations where alcoholic beverages are served, to detect a predetermined level of breath alcohol.
There is also a product for analyzing bad breath on the market, a portable sulfide monitor, popular with dentists (see The Science of Bad Breath in Scientific American, April, 2002, p. 78).